583,493 research outputs found

    Lessons from New Orleans: A Stronger Role for Public Defenders in Spurring Indigent Defense Reform

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    Excessive caseloads prevent public defenders from fulfilling their ethical obligations and curtail criminal defendants’ right to the effective assistance of counsel. Despite this ethical and constitutional dilemma, legislators have been reluctant to provide adequate funds for indigent defense. And because of the separation of powers, courts have been unable to force legislators’ hands. Against this backdrop, criminal defendants in states that choose not to adequately fund indigent defense face a serious risk of wrongful conviction. The Orleans Public Defenders Office (OPD) provides a case study of public defenders playing a stronger role in spurring legislative reform. In response to a funding crisis in Louisiana, the OPD refused to take new cases beyond constitutionally permissible workloads. This refusal resulted in criminal defendants being put on waiting lists for representation, which garnered national attention, gave rise to class action lawsuits against the state, and created a threat to public safety. These are governance problems that legislators prioritize over funding indigent defense. The OPD’s refusal to take new cases has been somewhat successful: in response to this crisis, the state legislature has provided additional funds to public defenders’ offices in the state. Public defenders are in a unique position to put pressure on legislators. By refusing to take new cases that would cause their workloads to be excessive, public defenders can both maintain their obligations to the profession and ensure constitutional representation for their clients

    DNA methylation analysis of the angiotensin converting enzyme (ACE) gene in major depression.

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    The angiotensin converting enzyme (ACE) has been repeatedly discussed as susceptibility factor for major depression (MD) and the bi-directional relation between MD and cardiovascular disorders (CVD). In this context, functional polymorphisms of the ACE gene have been linked to depression, to antidepressant treatment response, to ACE serum concentrations, as well as to hypertension, myocardial infarction and CVD risk markers. The mostly investigated ACE Ins/Del polymorphism accounts for ~40%-50% of the ACE serum concentration variance, the remaining half is probably determined by other genetic, environmental or epigenetic factors, but these are poorly understood. The main aim of the present study was the analysis of the DNA methylation pattern in the regulatory region of the ACE gene in peripheral leukocytes of 81 MD patients and 81 healthy controls. We detected intensive DNA methylation within a recently described, functional important region of the ACE gene promoter including hypermethylation in depressed patients (p = 0.008) and a significant inverse correlation between the ACE serum concentration and ACE promoter methylation frequency in the total sample (p = 0.02). Furthermore, a significant inverse correlation between the concentrations of the inflammatory CVD risk markers ICAM-1, E-selectin and P-selectin and the degree of ACE promoter methylation in MD patients could be demonstrated (p = 0.01 - 0.04). The results of the present study suggest that aberrations in ACE promoter DNA methylation may be an underlying cause of MD and probably a common pathogenic factor for the bi-directional relationship between MD and cardiovascular disorders

    Whey-derived peptides interactions with ACE by molecular docking as a potential predictive tool of natural ACE inhibitors

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    Several milk/whey derived peptides possess high in vitro angiotensin I-converting enzyme (ACE) inhibitory activity. However, in some cases, poor correlation between the in vitro ACE inhibitory activity and the in vivo antihypertensive activity has been observed. The aim of this study is to gain insight into the structure-activity relationship of peptide sequences present in whey/milk protein hydrolysates with high ACE inhibitory activity, which could lead to a better understanding and prediction of their in vivo antihypertensive activity. The potential interactions between peptides produced from whey proteins, previously reported as high ACE inhibitors such as IPP, LIVTQ, IIAE, LVYPFP, and human ACE were assessed using a molecular docking approach. The results show that peptides IIAE, LIVTQ, and LVYPFP formed strong H bonds with the amino acids Gln 259, His 331, and Thr 358 in the active site of the human ACE. Interestingly, the same residues were found to form strong hydrogen bonds with the ACE inhibitory drug Sampatrilat. Furthermore, peptides IIAE and LVYPFP interacted with the amino acid residues Gln 259 and His 331, respectively, also in common with other ACE-inhibitory drugs such as Captopril, Lisinopril and Elanapril. Additionally, IIAE interacted with the amino acid residue Asp 140 in common with Lisinopril, and LIVTQ interacted with Ala 332 in common with both Lisinopril and Elanapril. The peptides produced naturally from whey by enzymatic hydrolysis interacted with residues of the human ACE in common with potent ACE-inhibitory drugs which suggests that these natural peptides may be potent ACE inhibitors

    Attempto Controlled English (ACE)

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    Attempto Controlled English (ACE) allows domain specialists to interactively formulate requirements specifications in domain concepts. ACE can be accurately and efficiently processed by a computer, but is expressive enough to allow natural usage. The Attempto system translates specification texts in ACE into discourse representation structures and optionally into Prolog. Translated specification texts are incrementally added to a knowledge base. This knowledge base can be queried in ACE for verification, and it can be executed for simulation, prototyping and validation of the specification.Comment: 13 pages, compressed, uuencoded Postscript, to be presented at CLAW 96, The First International Workshop on Controlled Language Applications, Katholieke Universiteit Leuven, 26-27 March 199

    Angiotensin-converting enzyme insertion/deletion polymorphism does not influence the restenosis rate after coronary stent implantation

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    Background. Experimental studies have shown an activation of the angiotensin-converting enzyme (ACE) system as a response to endothelial injury. Recent publications have elucidated the hypothesis that the ACE gene polymorphism may influence the level of late luminal loss after coronary stent implantation. It is still unclear whether the polymorphism of the angiotensin gene is a major predictor of the extent of neointimal hyperplasia. In this multicenter study, we therefore tested the relationship between the ACE gene polymorphism and the restenosis rate after coronary stent implantation. Methods: As a substudy of the optimization with intracoronary, ultrasound (ICUS) to reduce stent restenosis (OPTICUS) study, we analyzed ACE serum levels and the ACE gene polymorphism in 154 patients at 9 different centers. All patients underwent elective coronary stent implantation in a stenosis of a major coronary vessel. Balloon inflations were repeated until a satisfactory result was achieved in on-line quantitative coronary angiography or ICUS fulfilling the OPTICUS study criteria. After follow-up of 6 months, all patients underwent reangiography tinder identical projections as the baseline procedure. A blinded quantitative analysis of the initial procedure as well as the follow-up examinations were performed by an independent core laboratory. ACE gene polymorphism and ACE serum activity were measured at the 6-month follow-up in a double-blinded setting. Results: With respect to the ACE gene polymorphism, there were three subgroups: DID genotype (48 patients), ID (83 patients) and 11 (23 patients). The subgroups did not differ in regard to age, gender, extent of coronary artery disease, stenosis length, initial degree of stenosis or degree of stenosis after stent implantation. In all, 39 patients (25.3%) had significant restenosis: 12 DD patients (25.0%), 18 ID patients (21.7%) and 9 II patients (39.1%) (odds ratio 2.164, 95% confidence interval 0.853-5.493). We obtained the following results for ACE serum levels: 0.53 mumol/l/s in the DD subgroup, 0.29 mumol/l/s in the ID

    Rethinking Responsibility for Patient Injury: Accelerated-Compensation Events, a Malpractice and Quality Reform Ripe for a Test

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    The accelerated-compensation events (ACE) approach in medical malpractice reform was studied. Reforms based on ACE best address the twin goals of making compensation more equitable and avoiding bad outcomes in medical care

    Comparison of Allen Carr's Easyway programme with a specialist behavioural and pharmacological smoking cessation support service: a randomized controlled trial.

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    BACKGROUND AND AIMS: A combination of behavioural and pharmacological support is judged to be the optimal approach for assisting smoking cessation. Allen Carr's Easyway (ACE) is a single-session pharmacotherapy-free programme that has been in operation internationally for 38 years. We compared the effectiveness of ACE with specialist behavioural and pharmacological support delivered to the national standard in England. DESIGN: A two-arm, parallel-group, single-blind, randomized controlled trial. SETTING: London, UK, between February 2017 and May 2018. PARTICIPANTS: A total of 620 participants (310 in ACE and 310 in the combined behavioural and pharmacological support condition) were included in the analysis. Adult (≥ 18 years) smokers wanting to quit were randomized in a 1 : 1 ratio. Mean age for the total sample was 40.8 years, with 53.4% being male. Participant baseline characteristics (ethnicity, educational level, number of previous quit attempts, nicotine dependence) were evenly balanced between treatment groups. INTERVENTION AND COMPARATOR: The intervention was the ACE method of stopping smoking. This centres on a 4.5-6-hour session of group-based support, alongside subsequent text messages and top-up sessions if needed. It aims to make it easy to stop smoking by convincing smokers that smoking provides no benefits for them. The comparator was a specialist stop smoking service (SSS) providing behavioural and pharmacological support in accordance with national standards. MEASUREMENTS: The primary outcome was self-reported continuous abstinence for 26 weeks from the quit/quit re-set date verified by exhaled breath carbon monoxide measurement < 10 parts per million (p.p.m.). Primary analysis was by intention to treat. Secondary outcomes were: use of pharmacotherapy, adverse events and continuous abstinence up to 4 and 12 weeks. FINDINGS: A total of 468 participants attended treatment (255 ACE versus 213 SSS, P < 0.05). Of those who did attend treatment, 100 completed 6-month measures (23.7% ACE versus 20.7% SSS). Continuous abstinence to 26 weeks was 19.4% (60 of 310) in the ACE intervention and 14.8% (46 of 310) in the SSS intervention [risk difference for ACE versus SSS 4.5% (95% confidence interval (CI) = -1.4 to 10.4%, odds ratio (OR) = 1.38)]. The Bayes factor for superiority of the ACE condition was 1.24. CONCLUSION: There was no clear evidence of a difference in the efficacies of the Allen Carr's Easyway (ACE) and specialist smoking cessation support involving behavioural support and pharmacotherapy
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